Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.
Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems ar ....Cellular Responses to Oxidative Damage: Cell Aging. The aim of this project is to identify the mechanisms by which oxidative stress and free radical damage cause cell aging. This work will make a significant contribution to our understanding of the aging process in cells by identifying the major reactive oxygen species that contribute to cell aging, which defence systems and antioxidants provide the greatest degree of protection, what damage accumulates as cells age and which genetic systems are activated as during the process.Read moreRead less
Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific kno ....Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific knockout techniques to study key cohesin regulators in Drosophila. These studies will provide us with novel insights into how multicellular organisms regulate the structure and stability of their chromosomes.Read moreRead less
Proteomic and Transcriptional Profiling of Cartilage. Gene expression and signalling pathways that regulate cartilage formation, and its orderly transition to bone, are poorly described. Our studies will, for the first time, combine two complementary cutting-edge approaches, protein identification by proteomic analysis, and mRNA profiling by microarray analysis, to define these pathways and develop a comprehensive catalogue of proteins and gene expression patterns during cartilage development a ....Proteomic and Transcriptional Profiling of Cartilage. Gene expression and signalling pathways that regulate cartilage formation, and its orderly transition to bone, are poorly described. Our studies will, for the first time, combine two complementary cutting-edge approaches, protein identification by proteomic analysis, and mRNA profiling by microarray analysis, to define these pathways and develop a comprehensive catalogue of proteins and gene expression patterns during cartilage development and bone formation. This information will provide insight into the regulation of cartilage differentiation, maturation and structure, and will provide a critical platform for the development of more sophisticated cartilage and bone biomaterials for improved tissue repair and regeneration.Read moreRead less
Regulation of Stress Hormone Receptors in the Brain. Our research will provide information on how the brain controls our response to stress and will allow the development of targeted strategies to reduce the possibility during chronic stress of the development of conditions such as anxiety and depression. This will improve mental health outcomes in Australia and add to Australia's economic and social stability.
Developmental Switches: Nuclear Transport and Spermatogenesis. We propose to test the novel hypothesis that changes in the nuclear import machinery are a key facet of cellular differentiation. We will investigate a new paradigm in developmental biology regarding whether differentiation is achieved, or can be directed, by altering transport of macromolecules, such as specific transcription factors, into the nucleus. This project will define changes in the nuclear import machinery that accomp ....Developmental Switches: Nuclear Transport and Spermatogenesis. We propose to test the novel hypothesis that changes in the nuclear import machinery are a key facet of cellular differentiation. We will investigate a new paradigm in developmental biology regarding whether differentiation is achieved, or can be directed, by altering transport of macromolecules, such as specific transcription factors, into the nucleus. This project will define changes in the nuclear import machinery that accompany germ and somatic cell differentiation in the developing and adult mammalian testis. This will be linked to changes in the function of key proteins acting within the nucleus using both in vitro and in vivo approaches.
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Molecular, genetic and cellular analysis of melanisation in human pigmentation. This investigation examines variations in the genes that determine human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of ....Molecular, genetic and cellular analysis of melanisation in human pigmentation. This investigation examines variations in the genes that determine human skin pigmentation and are likely to be associated with skin cancer risk. Our research program will form the basis of future diagnostics based on major genes that determine a persons skin type. Current skin cancer prevention strategies rely predominantly on broad spectrum campaigns that are aimed at increasing the general community awareness of the damaging effects of ultraviolet (UV) radiation. A better understanding of the genetic basis of UV-sensitive skin types will greatly enhance the targeting of such skin cancer-prevention campaigns, provide an understanding of changes that occur in skin pathology, and the mechanisms of sun induced tanning.Read moreRead less
The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Mic ....The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Microaerobes include some bacteria, archea and protozoa. Realisation of the widespread habitats and importance of microaerophiles, has led recently to a vigorous interest in understanding their physiology. Knowledge of the basic properties of microaerophily has potential applications to Environmental Microbiology, Agriculture, Industrial Microbiology, Veterinary Science and Medicine.Read moreRead less
Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases includ ....Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases including infectious disease, auto-immune disease and leukaemia, and thus a long-term outcome may be improved treatments for such disease. Read moreRead less
Progenitor cells within the peritoneal cavity. Implantation of a foreign object into the peritoneal cavity of animals recruits undifferentiated cells of bone marrow origin that encapsulate the free-floating object, then differentiate into myofibroblasts. When large pieces of myofibroblast capsule tissue are subsequently grafted into autologous artery, bladder or vas deferens, they develop the structure and morphology of that organ. We hypothesise that multipotent progenitor cells sequestered t ....Progenitor cells within the peritoneal cavity. Implantation of a foreign object into the peritoneal cavity of animals recruits undifferentiated cells of bone marrow origin that encapsulate the free-floating object, then differentiate into myofibroblasts. When large pieces of myofibroblast capsule tissue are subsequently grafted into autologous artery, bladder or vas deferens, they develop the structure and morphology of that organ. We hypothesise that multipotent progenitor cells sequestered to the peritoneal cavity can be manipulated to differentiate along smooth muscle and other pathways. The proposed project aims to identify the origin of these cells and characterise the transcriptional program that regulates their differentiation.Read moreRead less